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Lung Cancer Stages, Treatments and Targeted Therapies
Lung cancer can be treated through a combination of surgery, radiation, and chemotherapy depending on its stage. Ongoing research is leading to the development of more targeted therapies, showcasing increasing success in treatment options. The future of lung cancer treatment appears promising with these advancements.
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Lung Cancer Stages, Treatments and Targeted Therapies
- 1. Lung Cancer: Stages,Treatments and Targeted Therapies David Barbie, M.D. Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute Assistant Professor of Medicine, Harvard Medical School November 2, 2013
- 2. Lung Cancer Incidenceand Mortality in U.S. KRAS Mutation ~30% ~50% ~90%
- 3. Lung Cancer Stagesand Treatments
- 4. Lung Cancer Stagesand Treatments Stage 1: Localized
- 5. Lung Cancer Stagesand Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Surgery, +/-chemotherapy
- 6. Lung Cancer Stagesand Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Surgery, +/-chemotherapy Stage 3: Locally advanced Chemotherapy and radiation, +/- surgery
- 7. Lung Cancer Stagesand Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Brain Surgery, +/-chemotherapy Stage 3: Locally advanced Chemotherapy and radiation, +/- surgery Bone Stage 4: Advanced/metastatic Chemotherapy +/- palliative radiation Liver Adrenals
- 8. Oncogenes are theJammed Accelerators of Cancer Cells
- 11. BCR-ABL - BCR-ABL + Shtivelmanet al. Nature 1985;315:550 Daley et al. Science 1990;247:824 Buchdunger et al. Cancer Res 1996;56:100 Deininger et al. Blood 1997;90:3691 Druker, BJ. Nat Med 2009;15:1149
- 12. Lynch et al.NEJM 2004;350:2129 Paez et al. Science 2004;304:1497
- 13. Mok et al.NEJM 2009;361:947
- 14. Better than chemotherapy, buttumors become resistant after 10-12 months Mok et al. NEJM 2009;361:947
- 15. Genomic complexity oflung cancer CML Lung Adenocarcinoma http://www.path.cam.ac.uk http://www.utoronto.ca/cancyto
- 16. Lung Cancer Thenand Now Many different oncogenes can get jammed No known genotype 1984 - 2003 No known genotype 2004 Erlotinib X X 2009 Crizotinib 2012 Courtesy of Stephanie Cardarella, MD, DFCI Thoracic Oncology
- 17. Chemotherapy Targets the Engine,Targeted Therapy the Accelerator EGFR inhibitor ALK inhibitor BRAF inhibitor Carboplatin + Alimta or Taxol
- 18. DFCI Patient withNSCLC and BRAF mutation treated with Dabrafenib August 10, 2012 September 19, 2012 Courtesy of Stephanie Cardarella, MD, DFCI Thoracic Oncology
- 19. MSKCC Patient withNSCLC and BRAF mutation treated with Dabrafenib February 2012 June 2012 Courtesy of Gregory Riely, MD, Memorial Sloan-Kettering Cancer Center
- 20. KRAS is DifficultTo Target Directly KRAS inhibitor – failed clinical trials
- 21. Alternatives to TargetingKRAS 1. Block known downstream pathways (between pedal and engine) Also failing in clinical trials
- 22. Alternatives to TargetingKRAS 1. Block known downstream pathways (between pedal and engine) XX Also failing in clinical trials X X
- 23. Alternatives to TargetingKRAS 2. Use genomics to identify currently unknown pathways needed for survival (that keep car from crashing) TBK1
- 24. CYT387 Impairs Viabilityof Lung cancer Cells A549 Lung Cancer Cells DMSO CYT387 (5mM)
- 25. Activity of CYT387in Kras-driven Murine Lung Cancer Murine KRAS-Driven Lung Cancer CYT387 100mg/kg/d H Baseline H Week 16 Kwok Wong Travis Cohoon
- 26. Activity of CYT387in Kras-driven Murine Lung Cancer H E pA ST T3 A B Uee n ad t t r 2m 5 µ C 2m 5 µ D Tor an a t el e xe o 2m 5 µ E 2m 5 µ F C an Yl e To 2m 5 µ 2m 5 µ
- 27. Alternatives to TargetingKRAS Blocking multiple unique pathways
- 28. Alternatives to TargetingKRAS Blocking multiple unique pathways X X X X
- 29. Activity of CYT387in Kras-driven Murine Lung Cancer KrasLSL-G12D/WT;p53flox/flox model with established tumor burden *p<0.01 **p<0.0001 CYT387: 100 mg/kg/daily by oral gavage Selumetinib: 25 mg/kg/twice daily by oral gavage Kwok Wong Travis Cohoon
- 30. Activity of CYT387in Kras-driven Murine Lung Cancer KrasLSL-G12D/WT;p53flox/flox model with established tumor burden *p<0.01 **p<0.0001 Treatment well tolerated other than initial gavage trauma CYT387: 100 mg/kg/daily by oral gavage Selumetinib: 25 mg/kg/twice daily by oral gavage Kwok Wong Travis Cohoon
- 31. Immunotherapy – “ImmuneCheckpoint Blockade”
- 32. Immunotherapy – “ImmuneCheckpoint Blockade”
- 33. Immunotherapy – “ImmuneCheckpoint Blockade” PD-L1 PD-L1 PD-L1
- 34. Immunotherapy – “ImmuneCheckpoint Blockade” T cell T cell PD1 PD1 PD-L1 PD-L1 PD-L1 PD1 T cell
- 35. Immunotherapy – “ImmuneCheckpoint Blockade” T cell X T cell PD1 X PD1 PD-L1 PD-L1 PD-L1 T cell X PD1
- 36. Immunotherapy – “ImmuneCheckpoint Blockade” T cell PD-L1 targeted drugs T cell X PD1 X PD1 PD-L1 PD-L1 PD-L1 T cell X PD1
- 37. Immunotherapy – “ImmuneCheckpoint Blockade” T cell T cell PD1 PD1 PD1 T cell
- 38. Immunotherapy – “ImmuneCheckpoint Blockade” T cell T cell PD1 PD1 PD1 T cell
- 39. Summary • Lung cancercan be treated with a combination of surgery, radiation, and chemotherapy depending on the stage
- 40. Summary • Lung cancercan be treated with a combination of surgery, radiation, and chemotherapy depending on the stage • We continue to develop new ways to target lung cancer more directly, with increasing success
- 41. Summary • Lung cancercan be treated with a combination of surgery, radiation, and chemotherapy depending on the stage • We continue to develop new ways to target lung cancer more directly, with increasing success • With combinations of these new targeted therapies the future is very bright